Activity-dependent Regulation of Synaptic Vesicle Abundance

P.I. Maria Bykhovskaia
Collaborator Dr. J. Troy Littleton, Massachusetts Institute of Technology


Synaptic vesicle cycling is highly dynamic and plastic, and subtle disruptions in its regulation may contribute to severe neurological disorders, including schizophrenia, epilepsy, Huntington’s and Parkinson’s Disease. Although a number of molecular determinants of vesicle cycling at synaptic terminals have been identified, our understanding of how vesicle cycling contributes to plasticity remains sparse. Using the Drosophila neuromuscular junction (NMJ), the lab of Dr. Bykhovskaia has discovered a pathway of presynaptic enhancement that may enable a nerve terminal to sustain and enhance its activity upon intense stimulation. Specifically, it was found that vesicle abundance in synaptic boutons is regulated by activity, and that intense stimulation increases vesicle number in nerve terminals. Importantly, these results suggest a functional implication for this form of plasticity: enhanced activity upon a subsequent intense stimulation.  This project employs a combination of molecular biology and genetics, live confocal imaging, and electron microscopy to unravel the mechanisms by which the terminal regulates its vesicle numbers in response to activity. Further, the project will test whether the phenomenon observed at the Drosophila glutamatergic synapse could be also detected in the mammalian central or peripheral synapses.